This application describes a neuroanatomical research project designed to examine the question whether the output of the striatum is indeed, as thus far generally assumed, directed exclusively at components of the central motor system. Recent findings in this laboratory (Kelley et al, 1982) have led to the conclusion that a large and circumscript antero-ventromedial sector of the striatum is innervated selectively by various fiber systems of limbic origin. Preliminary further observations suggest that this limbic-afferented striatal sector projects selectively to a histochemically distinct anteroventral subdivision of the external segment of the globus pallidus, the so-called ventral pallidum, and that this pallidal subdivision may project in turn to several limbic structures, including the amygdala. The proposed research is designed as a systematic attempt to verify this tentative notion of a limbic component within the extrapyramidal circuitry. Its long-term significance is that it may contribute to a better understanding of the anatomical and histochemical substrates of mental disorder and/or diseases such as Huntington's chorea and Gilles de la Tourette's disease which straddle the border between Neurology and Psychiatry. The study will consist in a detailed autoradiographic analysis of the topography of the striatopallidal connection, followed by a similar analysis of the efferents of the ventral pallidum. The latter part of the study will require particular efforts to determine whether the ventral-pallidal efferents suggested by the autoradiographic findings indeed originate from pallidal neurons and not from non-pallidal neurons intruded into the ventral pallidum from neighboring cells groups. For this purpose, the use of combined strategies will be necessary, in particular the combination of histochemical methods for acetylcholinesterase with retrograde cell-labelling methods, and second, the combination of retrograde cell-labelling by horseradish peroxidase with lesion-induced degeneration of striatal efferents, at the level of the electron microscope. The study will be done in the rat, with some additional experiments in the monkey to test whether the findings in the rat are valid for the primate brain as well.